Objectives: To explore the effect of fentanyl on 50% effective dose (ED50) of emulsified isoflurane for hypnosis and to define the type of interaction between fentanyl and emulsified isoflurane during rat hypnosis.
Methods: 125 male adult Sprague-Dawley rats (240-300 g) were divided into 5 groups depending on the drugs administered via the tail vein. The up-and-down sequential allocation technique was used to determine ED50 of fentanyl in the loss of righting reflex. According to above experiment results, the up-and-down sequential allocation technique was also used to determine ED50 of emulsified isoflurane combined with different fentanyl dose of 7.2 microg/kg (1/4 ED50), 14.3 microg/kg (1/2 ED50) or 21.5 microg/kg (3/4 ED50), respectively, and also without the fentanyl in the loss of righting reflex. Fentanyl was administered intravenously for 20 s followed by emulsified isoflurane for 10 s. The interval between the two was 1.5 min in groups administered with both. ED50 was calculated by using Dixon-Mood method. The isobolographic and algebraic analyses were used to define the type of interaction between fentanyl and emulsified isoflurane.
Results: The body weight and sex of rats was not significantly different between the 5 groups. ED50 was (28.7 +/- 2.1) microg/kg (26.5-30.8 microg/kg) in the fentanyl group, (0.525 +/- 0.032) mL/kg in the fentanyl 7.2 microg/kg +/- isoflurane group, (0.108 +/- 0.019) mL/kg in the fentanyl 14.3 microg/kg+isoflurane group, (0.075 +/- 0.011) mL/kg in the fentanyl 21.5 microg/kg+isoflurane group and (0.670 +/- 0.054) mL/kg in the isoflurane group. The isobolographic analysis indicated that ED50 of isoflurane decreased progressively in a non-linear fashion in the presence of increasing dose of fentanyl. The isobolographic and algebraic analyses demonstrated that the combination use of fentanyl and emulsified isoflurane could produce a synergistic effect on hypnosis.
Conclusions: Fentanyl enhances the hypnotic effect induced by emulsified isoflurane. The administration of associating fentanyl with emulsified isoflurane produces a synergistic effect on rat hypnosis.